Sequence and structural features of the T-fold, an original tunnelling building unit

A similar fold has been found in four archetype enzymes that perform differ ent functions. This new fold has been named the T-fold because it is found in multimeric proteins crossed by a tunnel. The T-fold consists of an antip arallel beta-sheet of four sequential strands, and two antiparallel helices between the second and third strand, layered on the concave side of the be ta-sheet. The presently known T-fold proteins share a high structural simil arity (a mean of 1.4 HL root mean square (r.m.s.) deviation on the common c ore) while they only exhibit a low level of sequence identity (a mean of 10 .5% on the aligned regions), They bind to substrates belonging to the purin e or pterin families, and share a fold-related binding site with a glutamat e or glutamine residue anchoring the substrate and a lot of conserved inter actions. They also share a similar oligomerization mode: several T-folds jo in together to form a beta(2n)alpha(n) barrel, then two barrels join togeth er in a head-to-head fashion to made up the native enzymes. The T-fold has the characteristics of a globular domain, with a hydrophobic core and a cle arly defined topohydrophobic network. It defines a new class of common fold s or recurrent domains found in distantly related proteins. However, it is likely not stable in monomeric form and until now is only observed in assoc iation with other T-folds through multimerization. Proteins 2000;39:142-154 , (C) 2000 Wiley-Liss, Inc.